Enantioselective and Regiodivergent Functionalization of N‐Allylcarbamates by Mechanistically Divergent Multicatalysis

Abstract

A pair of mechanistically divergent multicatalytic reaction sequences has been developed consisting of nickel-catalyzed isomerization of N-allylcarbamates and subsequent phosphoric-acid-catalyzed enantioselective functionalization of the resulting intermediates. By appropriate selection of reaction partners, in situ generated imines and ene-carbamates are mechanistically partitioned to yield opposing functionalized products. Formal α-functionalization to give protected α-arylamines is achieved upon enantioselective Friedel-Crafts reaction with arene nucleophiles, whereas formal β-functionalization is achieved upon reaction with diarylimine electrophiles in an enantioselective Povarov-[4+2] cycloaddition.

Selecting Chiral BINOL‐Derived Phosphoric Acid Catalysts: General Model To Identify Steric Features Essential for Enantioselectivity

“…However, whether the reaction benefits from large proximal sterics or small depends on the sterics of the nucleophile. For smaller displaced nucleophiles, large proximal sterics are advantageous, disfavouring Type I E pathways 29, 33, 35, 36, 37, 38, 72, 73, 74, 75, 76, 77, 78. However, if the nucleophile is large, small proximal sterics are essential 32, 34, 39, 79, 80.…”

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

“…To further simplify the cycloaddition procedure, Moran and co‐authors [219] developed an integrated one‐pot process that includes the generation of N ‐propenylcarbamate dienophile 203 a (R 3 =Me) (see Scheme 75) in situ from available N ‐allylcarbamate in the presence of the NiCl 2 /TRIPHOS/Zn/HCO 2 H catalytic system and the subsequent chiral phosphoric acid ( R )‐ VIIIb catalyzed asymmetric Povarov reaction. However, diastereoselectivity ( dr 4:1–15:1) and enantioselectivity (74–88% ee ) in the tandem reaction were lower, which could be ascribed to a competitive non‐selective catalysis with residual formic acid.…”

Recent Developments in Enantioselective Multicatalyzed Tandem Reactions

“…On the basis of the lower cost of nickel catalysts in comparison with many other transition metals and its wide range of oxidation states, enantioselective nickel‐mediated transformations have blossomed in the last decade . Among them is an enantioselective domino isomerization/arylation reaction of N‐ Boc allyl carbamate 106 with unprotected indoles 107 described by Moran et al., in 2016 . The process was catalyzed by a combination of 10 mol% of NiCl 2 (dme) and the same quantity of chiral phosphoric acid catalyst 27 in acetonitrile as solvent, as depicted in Scheme .…”

“…The same catalyst system was applied by these authors to promote a tandem reaction between N‐ Cbz allyl carbamates 109 and aromatic imines 110 . In this case, the catalysts were employed sequentially.…”